Experimental pneumococcal pleural empyema model: The effect of moxifloxacin

Jacob Strahilevitz*, Avram Lev, Itzchak Levi, Eduard Fridman, Ethan Rubinstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Objectives: Pleural empyema is a serious complication of pneumonia, the optimal therapy of which is still unknown. The objective of this study was to evaluate the use of moxifloxacin in this condition. Methods: Pleural empyema was induced in rabbits by intrapleural administration of Pasteurella multocida (105-6 cfu) or turpentine (0.3 mL) followed 3 h later by instillation of Streptococcus pneumoniae (ATCC 49619) (106 cfu) into the pleural cavity. The MICs of moxifloxacin for S. pneumoniae and P. multocida were 0.4 and 0.05 mg/L, respectively. Starting 30 h following S. pneumoniae challenge intramuscular moxifloxacin 12.5 and 25 mg/kg was administered × 4 (every 12 h). Pleural empyema fluid samples were obtained for bacterial count at 12 h intervals following the first three moxifloxacin administrations. Moxifloxacin levels in pleural empyema and serum samples were obtained at 0, 30, 60, 120, 240, 360 and 480 min and 12 h after the 4th dose and determined by bioassay. Results: In control animals, S. pneumoniae(and P. multocida) persisted in the pleural empyema. S. pneumoniae also persisted in the pleural empyema fluid when moxifloxacin was administered at 12.5 mg/kg (×4 administrations). Mean serum and pleural empyema peak moxifloxacin levels (following the 25 mg/kg dose) were 7.6 (±3.2) and 4.8 (±2.5) mg/L, respectively. Pleural empyema peak moxifloxacin concentration lagged 1 h after serum moxifloxacin. Serum and pleural empyema half-lives were ∼1.5 and ∼6 h, respectively. Serum AUC1-12 was 29.4 (±6.8) mg-h/L and serum area under the inhibitory concentration curve (AUIC) was 73.5 mg·h/L. Pleural empyema AUC1-12 was 34.3 (±11.7) mg/L and pleural empyema AUIC was 85.8 mg·h/L. S. pneumoniae was eradicated from pleural empyema following a single dose of moxifloxacin 25 mg/kg in 52% of the animals and in 96% following four doses. Moxifloxacin was also effective in eradication of P. multocida. The rate of pleural empyema sterilization was related to moxifloxacin serum AUIC (r = 0.82) as well as serum peak moxifloxacin level (r = 0.84), but not to pleural empyema AUIC (r = 0.19) or pleural empyema peak levels. The results were similar for both methods of induction of pleural empyema. Conclusions: Moxifloxacin appears to penetrate well into experimental pleural empyema and effectively sterilize it from S. pneumoniae. Sterilization of S. pneumoniae is related to serum AUIC rather than to moxifloxacin pharmacokinetics in pleural empyema.

Original languageAmerican English
Pages (from-to)665-669
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume51
Issue number3
DOIs
StatePublished - 1 Mar 2003
Externally publishedYes

Keywords

  • Moxifloxacin
  • Pasteurella multocida
  • Pleural empyema
  • Streptococcus pneumoniae
  • Turpentine

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